Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci
Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined th...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Journal article |
| Publicado em: |
2014
|
| _version_ | 1826292346106413056 |
|---|---|
| author | Tragante, V Tragante, V Barnes, MR Ganesh, S Lanktree, M Guo, W Franceschini, N Smith, E Johnson, T Holmes, M Padmanabhan, S Karczewski, K Almoguera, B Barnard, J Baumert, J Chang, Y Elbers, C Elbers, C Farrall, M Farrall, M Fischer, M Gaunt, T Gho, J Gieger, C Goel, A |
| author_facet | Tragante, V Tragante, V Barnes, MR Ganesh, S Lanktree, M Guo, W Franceschini, N Smith, E Johnson, T Holmes, M Padmanabhan, S Karczewski, K Almoguera, B Barnard, J Baumert, J Chang, Y Elbers, C Elbers, C Farrall, M Farrall, M Fischer, M Gaunt, T Gho, J Gieger, C Goel, A |
| author_sort | Tragante, V |
| collection | OXFORD |
| description | Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10-7) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification. © 2014 The American Society of Human Genetics. |
| first_indexed | 2024-03-07T03:13:16Z |
| format | Journal article |
| id | oxford-uuid:b4ee0717-6e89-4223-bf6c-4d8e1a4f614d |
| institution | University of Oxford |
| last_indexed | 2024-03-07T03:13:16Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:b4ee0717-6e89-4223-bf6c-4d8e1a4f614d2022-03-27T04:29:47ZGene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related lociJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b4ee0717-6e89-4223-bf6c-4d8e1a4f614dSymplectic Elements at Oxford2014Tragante, VTragante, VBarnes, MRGanesh, SLanktree, MGuo, WFranceschini, NSmith, EJohnson, THolmes, MPadmanabhan, SKarczewski, KAlmoguera, BBarnard, JBaumert, JChang, YElbers, CElbers, CFarrall, MFarrall, MFischer, MGaunt, TGho, JGieger, CGoel, ABlood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10-7) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification. © 2014 The American Society of Human Genetics. |
| spellingShingle | Tragante, V Tragante, V Barnes, MR Ganesh, S Lanktree, M Guo, W Franceschini, N Smith, E Johnson, T Holmes, M Padmanabhan, S Karczewski, K Almoguera, B Barnard, J Baumert, J Chang, Y Elbers, C Elbers, C Farrall, M Farrall, M Fischer, M Gaunt, T Gho, J Gieger, C Goel, A Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci |
| title | Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci |
| title_full | Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci |
| title_fullStr | Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci |
| title_full_unstemmed | Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci |
| title_short | Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci |
| title_sort | gene centric meta analysis in 87 736 individuals of european ancestry identifies multiple blood pressure related loci |
| work_keys_str_mv | AT tragantev genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT tragantev genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT barnesmr genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT ganeshs genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT lanktreem genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT guow genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT franceschinin genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT smithe genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT johnsont genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT holmesm genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT padmanabhans genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT karczewskik genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT almoguerab genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT barnardj genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT baumertj genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT changy genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT elbersc genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT elbersc genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT farrallm genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT farrallm genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT fischerm genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT gauntt genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT ghoj genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT giegerc genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci AT goela genecentricmetaanalysisin87736individualsofeuropeanancestryidentifiesmultiplebloodpressurerelatedloci |